With the passage of the Family Prevention and Tobacco Control Act of 2009, the Federal Government has gained regulatory authority over the formulation and marketing of tobacco based products. Although a great deal of science is available to inform the FDA on the development and evaluation of conventional tobacco products, little science is available on electronic cigarettes. Appropriate regulatory policy for ENDS is currently hindered by the lack of data describing realistic use of these products and the resulting health impacts, including toxicity and abuse liability. Herein, our multidisciplinary tea proposes to establish comparative nicotine emissions and dosages between e-cigarettes and cigarettes, and to evaluate whether or not these doses result in toxicological responses in vivo in mice. In the proposed study, we test the hypothesis that electronic cigarette users are exposed to lower amounts of nicotine compared to conventional cigarettes, but that these exposure levels will induce toxic oxidative and inflammatory responses in vivo, and addiction comparable to that seen from smoking. Our specific aims are to (1) Determine how the constituents, components and design features of electronic cigarettes vary among different manufactures and how emissions are affected by consumer use behaviors, and (2) determine if e-cigarettes have toxic oxidative damage and pro inflammatory effects in vivo in mouse models similar to conventional cigarette smoke, and dependence potential and addictive properties of electronic cigarettes in mice after chronic e-cigarette exposures. Results of this study will impac consumer's decisions regarding the use and effectiveness of electronic cigarettes for nicotine replacement therapy. Currently, such consumer perceptions are being formed the without the benefit of independent scientific data. Furthermore, this study has broader implications on the nicotine-related disease mechanisms of smoking induced respiratory and cardiovascular diseases, and cancer. Overall, this proposal will determine the potential toxicity and health implications of harmful constituents present in electronic cigarettes, determine the toxicity of exposure, understand the dependence potential, and addictiveness of electronic cigarettes. This project will serve the FDA by generating relevant findings and data needed to inform the regulation of the manufacture, distribution, and marketing of electronic cigarettes, and ultimately provide the scientific data needed to determine if electronic cigarette use has a negative or positive impact on public health.